Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes. Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80–90% VO2reserve) separated by similar bouts of lower-intensity intervals (50–60% VO2reserve). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions. Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p < 0.001), and resting blood pressure and heart rate were both reduced (both p < 0.05). Postintervention disease activity was reduced by 38% (DAS28; p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p < 0.001) all increased following training. The frequency of cluster of differentiation 14-positive (CD14+)/CD16+ monocytes was reduced (p = 0.002), with both nonclassical (CD14dim/CD16bright) and intermediate (CD14bright/CD16positive) monocytes being reduced (both p < 0.05). Following training, the cell surface expression of intermediate monocyte Toll-like receptor 2 (TLR2), TLR4, and HLA-DR was reduced (all p < 0.05), and monocyte phagocytosis of E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1β, IL-6, CXCL-8, IL-10, CRP, or TNF-α. We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients. ClinicalTrials.gov, NCT02528344 . Registered on 19 August 2015.

Neutrophils and monocytes are key components of the innate immune system that undergo age‐associated declines in function. This study compared the impact of high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) on immune function in sedentary adults. Twenty‐seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO_2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO_2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune‐enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of sarcopenia, prolonged hospitalization, and loss of autonomy. Although several age-sensitive pathways have been identified, further investigation is needed to define targets of cellular dysfunction. Autophagy, a process of cellular catabolism, is emerging as a key regulator of muscle regeneration affecting stem cell, immune cell, and myofiber function. Muscle stem cell senescence is associated with a suppression of autophagy during key phases of the regenerative program. Macrophages, a key immune cell involved in muscle repair, also rely on autophagy to aid in tissue repair. This review will focus on the role of autophagy in various aspects of the regenerative program, including adult skeletal muscle stem cells, monocytes/macrophages, and corresponding age-associated dysfunction. Furthermore, we will highlight rejuvenation strategies that alter autophagy to improve muscle regenerative function.

Neutrophil dysfunction is a common feature of aging, and is associated with the pathogenesis of many age-related diseases, including type 2 diabetes mellitus (T2DM). Although exercise training improves metabolic health, decreases risk of T2DM, and is associated with improving neutrophil functions, involvement in regular physical activity declines with age. The aim of this study was to determine if neutrophil functions could be improved in association with changes in fitness and metabolic parameters in older adults at risk for T2DM using 10-weeks of low volume high-intensity interval exercise training (HIIT). Ten older (71 ± 5 years) sedentary adults with prediabetes (HbA1c: 6.1 ± 0.3%) completed 10 weeks of a supervised HIIT program. Three 30 min sessions/week consisted of ten 60 s intervals of low intensity [50–60% heart rate reserve (HRR)] separated with similar durations of high intensity intervals (80–90% HRR). Before and after training, glucose and insulin sensitivity, neutrophil chemotaxis, bacterial phagocytosis, reactive oxygen species (ROS) production, and mitochondrial functions were assessed. Exercise-mediated changes in cardiorespiratory fitness (VO_2peak) and neutrophil functions were compared to six young (23 ± 1 years) healthy adults. Following training, significant reductions in fasting glucose and insulin were accompanied by improved glucose control and insulin sensitivity (all p < 0.05). Before exercise training, VO_2peak in the old participants was significantly less than that of the young controls (p < 0.001), but increased by 16 ± 11% following training (p = 0.002) resulting in a 6% improvement of the deficit. Neutrophil chemotaxis, phagocytosis and stimulated ROS production were significantly less than that of the young controls, while basal ROS were higher before training (all p < 0.05). Following training, chemotaxis, phagocytosis and stimulated ROS increased while basal ROS decreased, similar to levels observed in the young controls (all p < 0.05) and reducing the deficit of the young controls between 2 and 154%. In five of the adults with prediabetes, neutrophil mitochondrial functions were significantly poorer than the six young controls before training. Following training, mitochondrial functions improved toward those observed in young controls (all p < 0.05), reducing the deficit of the young controls between 14.3 and 451%. Ten weeks of HIIT in older adults at risk for T2DM reduced disease risk accompanied by improved primary and bioenergetic neutrophil functions. Our results are consistent with a reduced risk of infections mediated by relationships in exercise induced systemic and cellular metabolic features. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02441205, registered on May 12th, 2015.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to improving CLL patients’ physical fitness and immune functions may be participation in a structured exercise program. The aims of this pilot study were to examine physical and immunological changes, and feasibility of a 12-week high-intensity interval training (HIIT) combined with muscle endurance-based resistance training on older adults with treatment naïve CLL. We enrolled eighteen participants with CLL aged 64.9 ± 9.1 years and assigned them to groups depending on distance lived from our fitness center. Ten participants (4 M/6F) completed HIIT and six participants (4 M/2F) completed a non-exercising control group (Controls). HIIT consisted of three 30-min treadmill sessions/week plus two concurrent 30-min strength training sessions/week. Physical and immunological outcomes included aerobic capacity, muscle strength and endurance, and natural killer (NK) cell recognition and killing of tumor cells. We confirmed feasibility if > 70% of HIIT participants completed > 75% of prescribed sessions and prescribed minutes, and if > 80% of high-intensity intervals were at a heart rate corresponding to at least 80% of peak aerobic capacity (VO_2peak). Results are presented as Hedge’s G effect sizes (g), with 0.2, 0.5 and 0.8 representing small, medium and large effects, respectively. Following HIIT, leg strength (g = 2.52), chest strength (g = 1.15) and seated row strength (g = 3.07) were 35.4%, 56.1% and 39.5% higher than Controls, respectively, while aerobic capacity was 3.8% lower (g = 0.49) than Controls. Similarly, following HIIT, in vitro NK-cell cytolytic activity against the K562 cell line (g = 1.43), OSU-CLL cell line (g = 0.95), and autologous B-cells (g = 1.30) were 20.3%, 3.0% and 14.6% higher than Controls, respectively. Feasibility was achieved, with HIIT completing 5.0 ± 0.2 sessions/week and 99 ± 3.6% of the prescribed minutes/week at heart rates corresponding to 89 ± 2.8% of VO_2peak. We demonstrate that 12-weeks of supervised HIIT combined with muscle endurance-based resistance training is feasible, and that high adherence and compliance are associated with large effects on muscle strength and immune function in older adults with treatment naïve CLL.Trial registration: NCT04950452.